LOCUS       NP_005916                701 aa            linear   PRI 28-APR-2025
DEFINITION  meprin A subunit beta isoform 1 precursor [Homo sapiens].
ACCESSION   NP_005916
VERSION     NP_005916.2
DBSOURCE    REFSEQ: accession NM_005925.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 701)
  AUTHORS   Siemsen,W., Halske,C., Behrens,H.M., Kruger,S., Becker-Pauly,C. and
            Rocken,C.
  TITLE     The putative pleiotropic functions of meprin beta in gastric cancer
  JOURNAL   Gastric Cancer 26 (4), 542-552 (2023)
   PUBMED   36976399
  REMARK    GeneRIF: The putative pleiotropic functions of meprin beta in
            gastric cancer.
REFERENCE   2  (residues 1 to 701)
  AUTHORS   Linnert,M., Fritz,C., Jager,C., Schlenzig,D., Ramsbeck,D.,
            Kleinschmidt,M., Wermann,M., Demuth,H.U., Parthier,C. and
            Schilling,S.
  TITLE     Structure and Dynamics of Meprin beta in Complex with a
            Hydroxamate-Based Inhibitor
  JOURNAL   Int J Mol Sci 22 (11), 5651 (2021)
   PUBMED   34073350
  REMARK    GeneRIF: Structure and Dynamics of Meprin beta in Complex with a
            Hydroxamate-Based Inhibitor.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 701)
  AUTHORS   Menon,P.K., Koistinen,N.A., Iverfeldt,K. and Strom,A.L.
  TITLE     Phosphorylation of the amyloid precursor protein (APP) at Ser-675
            promotes APP processing involving meprin beta
  JOURNAL   J Biol Chem 294 (47), 17768-17776 (2019)
   PUBMED   31604820
  REMARK    GeneRIF: As meprin beta cleavage of APP has been shown to result in
            formation of highly aggregation-prone, truncated Abeta2-40/42
            peptides, enhanced APP processing by this enzyme could contribute
            to Alzheimer's disease pathology.
REFERENCE   4  (residues 1 to 701)
  AUTHORS   Schaffler,H., Li,W., Helm,O., Kruger,S., Boger,C., Peters,F.,
            Rocken,C., Sebens,S., Lucius,R., Becker-Pauly,C. and Arnold,P.
  TITLE     The cancer-associated meprin beta variant G32R provides an
            additional activation site and promotes cancer cell invasion
  JOURNAL   J Cell Sci 132 (11) (2019)
   PUBMED   31076514
  REMARK    GeneRIF: The authors found that increased meprin beta G32R activity
            at the cell surface reduces cell proliferation, but increases cell
            invasion.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 701)
  AUTHORS   Wichert,R., Ermund,A., Schmidt,S., Schweinlin,M., Ksiazek,M.,
            Arnold,P., Knittler,K., Wilkens,F., Potempa,B., Rabe,B.,
            Stirnberg,M., Lucius,R., Bartsch,J.W., Nikolaus,S.,
            Falk-Paulsen,M., Rosenstiel,P., Metzger,M., Rose-John,S.,
            Potempa,J., Hansson,G.C., Dempsey,P.J. and Becker-Pauly,C.
  TITLE     Mucus Detachment by Host Metalloprotease Meprin beta Requires
            Shedding of Its Inactive Pro-form, which Is Abrogated by the
            Pathogenic Protease RgpB
  JOURNAL   Cell Rep 21 (8), 2090-2103 (2017)
   PUBMED   29166602
  REMARK    GeneRIF: This secreted cysteine protease potently converts
            membrane-bound meprin beta into its active form, impairing meprin
            beta shedding and its function as a mucus-detaching protease
REFERENCE   6  (residues 1 to 701)
  AUTHORS   Bankus,J.M. and Bond,J.S.
  TITLE     Expression and distribution of meprin protease subunits in mouse
            intestine
  JOURNAL   Arch Biochem Biophys 331 (1), 87-94 (1996)
   PUBMED   8660687
REFERENCE   7  (residues 1 to 701)
  AUTHORS   Bond,J.S., Rojas,K., Overhauser,J., Zoghbi,H.Y. and Jiang,W.
  TITLE     The structural genes, MEP1A and MEP1B, for the alpha and beta
            subunits of the metalloendopeptidase meprin map to human
            chromosomes 6p and 18q, respectively
  JOURNAL   Genomics 25 (1), 300-303 (1995)
   PUBMED   7774936
REFERENCE   8  (residues 1 to 701)
  AUTHORS   Yamaguchi,T., Fukase,M., Sugimoto,T., Kido,H. and Chihara,K.
  TITLE     Purification of meprin from human kidney and its role in
            parathyroid hormone degradation
  JOURNAL   Biol Chem Hoppe Seyler 375 (12), 821-824 (1994)
   PUBMED   7710697
REFERENCE   9  (residues 1 to 701)
  AUTHORS   Kaushal,G.P., Walker,P.D. and Shah,S.V.
  TITLE     An old enzyme with a new function: purification and
            characterization of a distinct matrix-degrading metalloproteinase
            in rat kidney cortex and its identification as meprin
  JOURNAL   J Cell Biol 126 (5), 1319-1327 (1994)
   PUBMED   8063866
REFERENCE   10 (residues 1 to 701)
  AUTHORS   Dumermuth,E., Eldering,J.A., Grunberg,J., Jiang,W. and Sterchi,E.E.
  TITLE     Cloning of the PABA peptide hydrolase alpha subunit (PPH alpha)
            from human small intestine and its expression in COS-1 cells
  JOURNAL   FEBS Lett 335 (3), 367-375 (1993)
   PUBMED   8262185
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AY695931.1 and X81333.1.
            
            On Jul 24, 2007 this sequence version replaced NP_005916.1.
            
            Summary: Meprins are multidomain zinc metalloproteases that are
            highly expressed in mammalian kidney and intestinal brush border
            membranes, and in leukocytes and certain cancer cells. They are
            involved in the hydrolysis of a variety of peptide and protein
            substrates, and have been implicated in cancer and intestinal
            inflammation. Mature meprins are oligomers of evolutionarily
            related, but separately encoded alpha and/or beta subunits.
            Homooligomers of alpha subunit are secreted, whereas, oligomers
            containing the beta subunit are plasma membrane-bound. This gene
            encodes the beta subunit. Targeted disruption of this gene in mice
            affects embryonic viability, renal gene expression profiles, and
            distribution of the membrane-associated alpha subunit in kidney and
            intestine. [provided by RefSeq, Oct 2011].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AY695931.1, BC144244.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968540, SAMEA2144835
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000269202.11/ ENSP00000269202.6
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..701
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="18"
                     /map="18q12.1"
     Protein         1..701
                     /product="meprin A subunit beta isoform 1 precursor"
                     /EC_number="3.4.24.63"
                     /note="endopeptidase-2; PABA peptide hydrolase; PPH beta;
                     N-benzoyl-L-tyrosyl-p-amino-benzoic acid hydrolase beta
                     subunit; N-benzoyl-L-tyrosyl-P-amino-benzoic acid
                     hydrolase subunit beta; meprin B; meprin A, beta"
                     /calculated_mol_wt=77052
     sig_peptide     1..22
                     /inference="COORDINATES: ab initio prediction:SignalP:6.0"
                     /calculated_mol_wt=2538
     Region          26..255
                     /region_name="ZnMc_meprin"
                     /note="Zinc-dependent metalloprotease, meprin_like
                     subfamily. Meprins are membrane-bound or secreted
                     extracellular proteases, which cleave a variety of
                     targets, including peptides such as parathyroid hormone,
                     gastrin, and cholecystokinin, cytokines such as...;
                     cd04282"
                     /db_xref="CDD:239809"
     mat_peptide     62..701
                     /product="Meprin A subunit beta. /id=PRO_0000028884"
                     /note="propagated from UniProtKB/Swiss-Prot (Q16820.3)"
                     /calculated_mol_wt=72659
     Site            order(146,184,213)
                     /site_type="active"
                     /note="putative substrate specificity determinants
                     [active]"
                     /db_xref="CDD:239809"
     Site            order(152..153,156,162)
                     /site_type="active"
                     /db_xref="CDD:239809"
     Site            218
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22988105; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Site            238
                     /site_type="other"
                     /note="Mediates preference for acidic residues at subsite
                     P1'; propagated from UniProtKB/Swiss-Prot (Q16820.3)"
     Site            254
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22988105; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Region          265..428
                     /region_name="MAM"
                     /note="MAM domain, meprin/A5/mu; pfam00629"
                     /db_xref="CDD:459878"
     Site            370
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22988105; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Site            421
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Region          427..586
                     /region_name="MATH"
                     /note="MATH (meprin and TRAF-C homology) domain; an
                     independent folding unit with an eight-stranded
                     beta-sandwich structure found in meprins, TRAFs and other
                     proteins. Meprins comprise a class of extracellular
                     metalloproteases which are anchored to the membrane...;
                     cl02446"
                     /db_xref="CDD:445786"
     Site            436
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22988105; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Site            445
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22988105; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Site            order(476,556..558)
                     /site_type="other"
                     /note="putative substrate binding site [chemical binding]"
                     /db_xref="CDD:238068"
     Site            547
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22988105; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Site            592
                     /site_type="glycosylation"
                     /note="N-linked (GlcNAc...) asparagine.
                     /evidence=ECO:0000269|PubMed:22988105; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Site            593
                     /site_type="glycosylation"
                     /note="O-linked (GalNAc...) serine. /evidence=ECO:0000255;
                     propagated from UniProtKB/Swiss-Prot (Q16820.3)"
     Site            594
                     /site_type="glycosylation"
                     /note="O-linked (GalNAc...) threonine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Region          595..607
                     /region_name="Required for proteolytic processing"
                     /note="propagated from UniProtKB/Swiss-Prot (Q16820.3)"
     Site            599
                     /site_type="glycosylation"
                     /note="O-linked (GalNAc...) threonine.
                     /evidence=ECO:0000255; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     Site            603
                     /site_type="glycosylation"
                     /note="O-linked (GalNAc...) serine. /evidence=ECO:0000255;
                     propagated from UniProtKB/Swiss-Prot (Q16820.3)"
     Site            653..673
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q16820.3)"
     Site            694
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0000269|PubMed:34125978; propagated from
                     UniProtKB/Swiss-Prot (Q16820.3)"
     CDS             1..701
                     /gene="MEP1B"
                     /coded_by="NM_005925.3:33..2138"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1"
                     /db_xref="CCDS:CCDS45846.1"
                     /db_xref="GeneID:4225"
                     /db_xref="HGNC:HGNC:7020"
                     /db_xref="MIM:600389"
ORIGIN      
        1 mdlwnlswfl fldallvisg latpenfdvd ggmdqdifdi neglgldlfe gdirldraqi
       61 rnsiigekyr wphtipyvle dslemnakgv ilnaferyrl ktcidfkpwa getnyisvfk
      121 gsgcwssvgn rrvgkqelsi gancdriatv qheflhalgf wheqsrsdrd dyvrimwdri
      181 lsgrehnfnt ysddisdsln vpydytsvmh ysktafqngt eptivtrisd fedvigqrmd
      241 fsdsdllkln qlyncsssls fmdscsfele nvcgmiqssg dnadwqrvsq vprgpesdhs
      301 nmgqcqgsgf fmhfdsssvn vgatavlesr tlypkrgfqc lqfylynsgs esdqlniyir
      361 eysadnvdgn ltlveeikei ptgswqlyhv tlkvtkkfrv vfegrkgsga slgglsiddi
      421 nlsetrcphh iwhirnftqf igspngtlys ppfysskgya fqiylnlahv tnagiyfhli
      481 sganddqlqw pcpwqqatmt lldqnpdirq rmsnqrsitt dpfmttdngn yfwdrpskvg
      541 tvalfsngtq frrgggygts afitherlks rdfikgddvy illtvedish lnstqiqltp
      601 apsvqdlcsk ttckndgvct vrdgkaecrc qsgedwwymg ercekrgstr dtiviavsst
      661 vavfalmlii tlvsvyctrk kyrermssnr pnltpqnqha f
//
